Bio

Academic Appointments


  • Clinical Instructor, Radiology

Publications

All Publications


  • A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition CELL STEM CELL Goff, D. J., Recart, A. C., Sadarangani, A., Chun, H., Barrett, C. L., Krajewska, M., Leu, H., Low-Marchelli, J., Ma, W., Shih, A. Y., Wei, J., Zhai, D., Geron, I., Pu, M., Bao, L., Chuang, R., Balaian, L., Gotlib, J., Minden, M., Martinelli, G., Rusert, J., Dao, K., Shazand, K., Wentworth, P., Smith, K. M., Jamieson, C. A., Morris, S. R., Messer, K., Goldstein, L. S., Hudson, T. J., Marra, M., Frazer, K. A., Pellecchia, M., Reed, J. C., Jamieson, C. H. 2013; 12 (3): 316-328

    Abstract

    Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcriptome RNA sequencing, splice-isoform-specific quantitative RT-PCR (qRT-PCR), nanoproteomics, stromal coculture, and BC LSC xenotransplantation analyses. Cumulatively, these studies show that the alternative splicing of multiple prosurvival BCL2 family genes promotes malignant transformation of myeloid progenitors into BC LSCS that are quiescent in the marrow niche and that contribute to therapeutic resistance. Notably, sabutoclax, a pan-BCL2 inhibitor, renders marrow-niche-resident BC LSCs sensitive to TKIs at doses that spare normal progenitors. These findings underscore the importance of alternative BCL2 family splice-isoform expression in BC LSC maintenance and suggest that the combinatorial inhibition of prosurvival BCL2 family proteins and BCR-ABL may eliminate dormant LSCs and obviate resistance.

    View details for DOI 10.1016/j.stem.2012.12.011

    View details for Web of Science ID 000329569400010

    View details for PubMedID 23333150

  • Sabutoclax, a Novel Pan BCL2 Family Inhibitor, Sensitizes Dormant Blast Crisis Chronic Myeloid Leukemia Stem Cells to Dasatinib 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Leu, H. S., Goff, D. J., Low-Marchelli, J., Recart, A. C., Smith, K. M., Ma, W., Sadarangani, A., Shih, A. Y., Wei, J., Zhai, D., Gotlib, J., Minden, M. D., Martinelli, G., Marra, M. A., Frazer, K. A., Pellecchia, M., Reed, J. C., Jamieson, C. AMER SOC HEMATOLOGY. 2012
  • BCL2 Splice Isoform Switching Promotes Leukemia Stem Cell Survival and Sensitivity to a Novel Pan BCL2 Inhibitor 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Goff, D., Smith, K. M., Shih, A. Y., Court-Recart, A., Sadarangani, A., Geron, I., Chuang, R., Balaian, L., Wei, J., Kitada, S., Zhai, D., Gotlib, J., Minden, M. D., Martinelli, G., Schairer, A., Leu, H., Ma, W., Jiang, Q., Rusert, J., Dao, K. T., Shazand, K., Volar, M., De Borja, R., McPherson, J. D., Hudson, T. J., Barrett, C. L., Frazer, K. A., Wentworth, P., Jamieson, C., Morris, S. R., Goldstein, L. S., Pellechia, M., Reed, J. C., Jamieson, C. AMER SOC HEMATOLOGY. 2011: 1176?76
  • Cycling Toward Leukemia Stem Cell Elimination Wtih a Selective Sonic Hedgehog Antagonist Shih, A. Y., Schairer, A., Barrett, C. L., Geron, I., Recart, A., Goff, D., Prashad, S., Wu, J., Jiang, Q., Gotlib, J., Balaian, L., Minden, M. D., Leu, H., Wall, R., Ma, W., Shazand, K., McPherson, J. D., Kornblau, S. M., Deichaite, I., Pu, M., Bao, L., Martinelli, G., Reya, T., Morris, S. R., VanArsdale, T., Hudson, T. J., Messer, K., Mikkola, H., Levin, W. J., Frazer, K. A., Sadarangani, A., Jamieson, C. AMER SOC HEMATOLOGY. 2011: 1613
  • Inhibition of JAK2 V617F-Induced erythroid skewing of hematopoietic stem cell differentiation with a selective JAK2 antagonist. 48th Annual Meeting of the American-Society-of-Hematology Geron, I., Barroga, C., Gotlib, J., Kavalerchik, E., Abrahamsson, A., Goff, D., Cacalano, N., Hood, J., Soll, R., Noronha, G., Tefferi, A., Weissman, I. L., Kaushansky, K., Jamieson, C. AMER SOC HEMATOLOGY. 2006: 1033A?1033A
  • Aberrant regulation of Wnt/beta-catenin pathway mediators in chronic myelogenous leukemia stem cells 48th Annual Meeting of the American-Society-of-Hematology Abrahamsson, A., Geron, I., Gotlib, J., Durocher, J., Creusot, R., Kavalerchik, E., Goff, D., Fathman, C. G., Lilleberg, S. L., Giles, F., Weissman, I., Jamieson, C. AMER SOC HEMATOLOGY. 2006: 605A?605A
  • Inhibition of chronic myelogenous leukemia stem cells with novel wnt antagonists. 48th Annual Meeting of the American-Society-of-Hematology Kavalerchik, E., Gotlib, J., Geron, I., Abrahamsson, A., Wrasidlo, W., Goff, D., Lu, D., Molinski, T., Giles, F., Weissman, I., Carson, D., Jamieson, C. AMER SOC HEMATOLOGY. 2006: 74A?75A

Footer Links:

Stanford Medicine Resources: